Our aim is to understand the cellular mechanisms through which L1-CNTNs affect this wide variety of processes. Our current work is focussed particularly on the role of NrCAM in regulating the Sonic Hedgehog (SHH) pathway in medulloblastoma (Sakurai et al., 2001; Xenaki et al., 2011) and in neural stem cells (Bizzoca et al., 2012), with a specific emphasis on its role in controlling the trafficking of SHH pathway components into and out of primary cilia.

Appointed adviser on genetics and biotechnology to EU-wide consortium (PRIVILEGED) determining the ethical and legal interests in privacy and data protection for research involving the use of genetic databases and bio-banks, 2007. www.privilegedproject.eu

The Cell Biology of Signal Modulation in Neural Development and Cancer

In biology context is everything. We aim to understand how cellular context alters the responses of cells to intercellular signals, focussing on the role of the L1-contactin ‘adhesion’ molecules (L1-CNTNs) in neural development. We have shown L1-CNTNs to modulate signals as diverse as semaphorins and hedgehogs (HHs) by altering the intracellular trafficking of their receptors during signalling. Our work on L1-CNTN modulation of Sema signalling during the wiring of mouse spinal sensory circuits (1) has converged on our studies showing F3/contactin repression of Sonic HH-stimulated proliferation of cerebellar neuron progenitors (2) to focus on a potential role for NrCAM in the trafficking of SHH signalling pathway components in the primary cilium. We are collaborating with Cadby (Physics) to develop STORM super resolution microscopy to follow this in real time. Collaborations with Clifford (Newcastle) reveal NrCAM to be upregulated in SHH group medulloblastomas and loss of NrCAM in vivo affects the penetrance of neoplasia in the Ptch1 mouse medulloblastoma model.

Roles for NrCAM in hypothalamic stem cell behaviour and for TAG1 in autism and obesity (3) are also being investigated with Placzek (Bateson), Markx (NY) and Buchner (Ohio) respectively, while with Whyte, Walmsley (Edinburgh) and Renshaw (Bateson) we are investigating semaphorins in neutrophil function.

I also have a particular interest in the use of animals in research, which relates to my masters Bioethics teaching (with Townend, Maastricht), and am the Sheffield lead in an FP7 project (ANIMPACT) aimed at evaluating the impact of Directive 2010/63/EU on animal welfare and research competitiveness in member states.

External Collaborators

Prof. Steve Clifford, Newcastle

Prof. Moira Whyte & Dr Sarah Walmsley, Edinburgh

Prof. Gianfrano Gennarini, Bari, Italy

Prof. David Townend, Maastricht, Netherlands

Dr Sander Markx, Columbia, NY, USA

Dr David Buchner, Case Western, Ohio, USA

Dr Avihu Klar, Hebrew University, Israel

Dr David Beier, Harvard Medical School, Boston, USA

Funding

Brain Tumour Support across Yorkshire

FP7

HEFCE

Teaching

Undergraduate and postgraduate taught modules

Undergraduate

BMS109-153 Neuroscience

BMS243/249 Developmental Neurobiology

BMS381 Developmental Neurobiology (Co-ordinator)

BMS382 Stem Cell Biology

Level 3 Practical and Dissertation Modules

Masters (MSc)

BMS6054 - Ethics, the Law and Public Awareness of Science (Co-ordinator)